1. Field
The following description relates to a method of preventing or treating glioma by inhibiting expression of Tarbp2, which is a novel transcription factor inducing Notch signal activation, and more specifically, to a pharmaceutical composition for treating glioma using shRNA or siRNA as a Tarbp2 (Tar RNA binding protein 2) expression inhibitor, a method of treating glioma using the same and use thereof. The following description also relates to a pharmaceutical composition, which contains a novel transcription factor inducing Notch signal activation as an active component, for treating a tumor of the central nervous system such as a brain tumor or spinal tumor and to a method for treating glioma. Specifically, the following description relates to a pharmaceutical composition for treating glioma using Tar RNA binding protein 2 (Tarbp2) genes or proteins, and to a method and use of treating a brain tumor or spinal tumor such as glioma using the same.
2. Discussion of Related Art
Notch is a cell surface receptor that performs important functions during development stages by regulating cell division, apoptosis, differentiation, and the like in metazoans, and has a membrane protein structure. The term “Notch” is derived from genes that induce an excessive growth of a wing of drosophila in mutations and cause notches of the wing, and is a signal system for fast signal transduction and amplification between cells in multicellular organisms.
Notch sends a signal caused by cell-to-cell contact through ligands such as Delta-like 1 and Jagged attached to cells. When Notch proteins and these ligands are bound, the Notch proteins are cut by ADAM metalloprotease and γ-secretase complex. Out of the cut parts, a Notch intracellular domain (NICD) corresponding to an intracellular domain enters into a nucleus, interacts with C-promoter Binding Factor 1 (CBF1), which is a DNA binding protein, and activates or inhibits transcription of downstream genes such as Hairy/Enhancer of Split (HES). In this case, HES is one of the transcription factors that are expressed when a Notch pathway is activated as an effector of Notch signaling, and an HES family includes Hes1, Hes3, Hes5, and the like.
Research on many factors associated with Notch signaling is important for analyzing causes of various human diseases and finding treatment methods thereof. In particular, research has reported that mutations in which transcription reactions of such signaling pathways are structurally activated frequently occur in several types of cancer. Therefore, importance of pathological roles of signaling pathways such as Hedgehog and Notch is emerging.
Meanwhile, glioma is known as one of the deadly forms of cancer affecting adults. Glioma is a malignant tumor occurring in a brain or spinal cord, and occupies about 50% of primary brain tumors. About 50% of glioma patients have a very short survival time (median survival time of 12 to 16 months). Since glioma is cancer that may originate in the human brain, surgical operation is difficult, it is difficult to distinguish the glioma from normal cells, it has strong permeability and mobility, and a survival rate of patients is low. The stronger the mobility and permeability, the faster the metastasis, and tissues surrounding the cancer do not function, which causes death. Accordingly, regulation of such mobility and invasiveness will serve as an important point of a therapeutic strategy for glioma.
Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC.
Recently, demand for research on a brain tumor or spinal tumor such as glioma, and development of a therapeutic agent, has increased. However, a specific research model and method has not yet been established, and a molecular mechanism underlying these diseases has not been well-known.